The prenatal diagnosis of genetic disease allows at-risk couples the option of having only unaffected offspring. The most commonly used approaches to prenatal diagnosis result in a diagnosis being made in the late first or second trimester of pregnancy. If an affected fetus is diagnosed, the couple is faced with the option of a termination of pregnancy, with its attendant medical and psychological trauma. Prenatal diagnosis of the pre-implantation embryo would allow at- risk couples to only have unaffected embryos transferred by in- vitro fertilization. Animal work has demonstrated the feasibility of pre-implantation diagnosis, although considerable species differences exist. The mouse model is especially useful in this area because of its similar pre-implantation developmental stages as compared to the human. This proposal is to develop pre-implantation embryonic biopsy techniques in beta-glucuronidase deficient mice. The biopsied embryos will then be transferred to host mothers and newborns will be assayed for confirmation of the prenatal diagnosis. Micro assay techniques will be developed to directly analyze the small numbers of cells obtained. The principal investigator in this study has been trained as an obstetrician with subspeciality training in maternal-fetal medicine and medical genetics. Very few obstetricians have taken medical genetics fellowships and it is the goal of this investigator to pursue a career in academic reproductive genetics. Much of the investigative work to date in obstetrics has been on whole animal models. This proposal is an attempt to utilize basic biochemical techniques to explore unanswered questions in pre-implantation development. The proposed work will be carried out in the reproductive genetics laboratories at the University of California, San Francisco. The sponsor of the project will be Mitchell S. Golbus, M.D., who is a recognized leader in the field of reproductive genetics.